Structure and method for synthesizing and using dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine and its tetrafluoroborate

ABSTRACT

The current invention relates to the structure, synthesis of dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate, as well as its applications in the palladium catalyzed carbon-chlorine bond activation for Suzuki coupling reactions and carbon-nitrogen bond formation reactions. The dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate could coordinate with the palladium catalyst to activate the inert carbon-chlorine bond highly selectively and catalyze Suzuki coupling reaction with arylboronic acid or carbon-nitrogen bond formation reaction with organic amines. The current invention uses only one step to synthesize dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine and its tetrafluoroborate is stable in the air. Compared with known synthetic routes of ligands used in activating carbon-chlorine bonds, the method of current invention is short, easy to operate. Moreover, with this type of ligands, the Suzuki coupling products of optically active chlorolactones and arylboronic acids would maintain their configuration and optical purity.

TECHNICAL FIELD

The current invention relates to the structure, a simple one stepsynthesis of dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate, as well as its applications in the Suzuki couplingreactions and the carbon-nitrogen bond formation reactions afterpalladium catalyzed carbon-chlorine bond activation reactions. To bemore specific, during the synthesis of stable dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate, the highly activeorganic phosphine is used to coordinate with the palladium catalyst inorder to activate the inert carbon-chlorine bond highly selectively.

BACKGROUND TECHNOLOGY

Organic halides are very important building blocks in organic synthesis.However, in their application in the past, expensive but relativelyactive organic bromides and iodides were used in coupling reactions tosynthesize target molecules (Chem. Rev. 1994, 94, 1047). If inertcarbon-chlorine bonds can be selectively activated and to use cheapchlorides in these types of reactions, it would be much better not onlyin respect of atom economy but also in respect of industrial cost. Sofar, some organic phosphine ligands can be used to activate inertcarbon-chlorine bonds (Angew. Chem. Int. Ed. 2002, 41, 4176; Acc. Chem.Res. 2007, 40, 275; Acc. Chem. Res. 2007, 40, 676; Acc. Chem. Res. 2008,41, 1461; Eur. J. Org. Chem. 2008, 2013; Angew. Chem. Int. Ed. 2008, 47,6338). However, during the study on the carbon-chlorine bond couplingreactions of the optically active β-chloro-α,β-unsaturated five-memberedlactones, the inventor of the current invention has discovered that someligands commonly used in the activation of carbon-chlorine bonds (suchas: tricyclohexylphosphonium tetrafluoroborate or2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl etc.) cannot yield thecorresponding optically active coupling products highly selectively(please see embodiments for specific examples).

SUMMARY OF THE INVENTION

The object of the current invention is to provide a new type of organicphosphine ligand—-dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine and itstetrafluoroborate as well as the method of their preparation.

Another goal of the current invention is to provide a method andapplication for the inert sp² carbon-chlorine bonds activations highlyselectively in the presence of the palladium catalyst and the abovementioned organic phosphine or its tetrafluoroborate.

The coordination of dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate with palladium catalyst can activate inertcarbon-chlorine bonds highly selectively, and can catalyze Suzukicoupling reaction with arylboronic acid, or carbon-nitrogen bondformation reaction with organic amines. Compared with known syntheticroutes of ligands used in activating carbon-chlorine bonds, the methodof current invention is short, easy to operate, which has undoubtedlyhigh research and application value.

The structures of the dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine andits tetrafluoroborate of the current invention are as follows:

wherein, R¹, R² is isopropyl, tertbutyl, cyclopropyl, cyclopentyl,cyclohexyl or admantyl group and R³ is alkyl group.

In the method to synthesize dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphineor its tetrafluoroborate of the current invention, trichlorophosphine,alkylmagnesium chloride, alkoxybenzene and n-butyl lithium are used asstarting materials. 1,3- or 1,3,5-alkoxybenzene is reacted with n-butyllithium in tetrahydrofuran to produce the corresponding lithium reagent.Alkylmagnesium chloride is reacted with trichlorophosphine to producechlorodialkyl phosphine. The above mentioned lithium reagent is reactedwith chlorodialkyl phosphine to produce dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine. Tetrafluoroboric acid aqueous solution canbe used to quench the reaction to produce the corresponding puredialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine tetrafluoroborate afterre-crystallization.

More detailed reaction steps are described as follows:

-   -   1) use tetrahydrofuran as an organic solvent, and at room        temperature, alkoxybenzene (R³O)_(n)C₆H_((6-n)) is reacted with        n-butyl lithium for 2-15 hours to produce the corresponding        lithium reagent (R³O)_(n)C₆H_((5-n))Li;    -   2) react the lithium reagent above (R³O)_(n)C₆H_((5-n))Li with        chlorodialkyl phosphine R¹R²PCl under-78-30° C. for 2 to 10        hours to produce a dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine        (R³O)_(n)C₆H_((5-n))P R¹R², tetrafluoroboric acid aqueous        solution is used to quench the reaction and to produce the        corresponding dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine        tetrafluoroborate ((R³O)_(n)C₆H_((5-n))P R¹R²)(H⁺BF₄ ⁻); the        molar ratio of said chlorodialkyl phosphine and (2,4,6- or        2,6-alkoxyphenyl) lithium is 0.8-1.2:1; said R¹, R² and R³ are        as described before. The reaction products can be purified by        re-crystallization.

A typical reaction formula is as follows:

In the reaction, R¹, R² is isopropyl, tertbutyl, cyclopropyl,cyclopentyl, cyclohexyl or admantyl group and R³ is alkyl group.

Dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine and its tetrafluoroborateof the current invention can be used in the selective activation ofinert carbon-chlorine bond for Suzuki coupling reaction to producebiphenyl compounds.

The more detailed description of the above mentioned application is asfollows: The synthesis of the coupling compounds are carried out underthe protection of inert gases, at 80-120° C., in an organic solvent,with the dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate and palladium as catalysts, arylboronic acid, base,water and arylchloride are reacted for 0.6-28 hours to produce thecorresponding biphenyl compounds; said organic solvent is 1,4-dioxane ortoluene; the equivalent molar ratio of base, palladium catalyst,dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,arylboronic acid, water and arylchloride is2.0˜4.0:0.03˜0.05:0.06˜0.10:1.5˜2.5:0˜5.0:1.0; said organic solvent is1,4-dioxane or toluene; said base is potassium carbonate, potassiumphosphate, cesium carbonate, or cesium fluoride; dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate is as claimed inclaim 1; said arylchloride is R⁴ substituted chlorobenzene; saidarylboronic acid is R⁵ substituted aryl boronic acid; R⁴ is ortho-,meta-, para-substituted alkyl, alkoxy or hydrogen; R⁵ is ortho-, meta-,para-substituted alkyl, alkoxy, aryl or hydrogen.

Alternatively, the synthesis of the coupling compounds is carried outunder the protection of inert gases, the reaction temperature is 80-120°C., toluene is the solvent, palladium acetate, dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate, potassiumcarbonate, arylboronic acid and optically active chlorolactone undergoreaction for 5-60 minutes and the corresponding coupling opticallyactive lactone compounds are obtained; the equivalent molar ratio ofsaid palladium acetate, dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine orits tetrafluoroborate, potassium carbonate, arylboronic acid andoptically active chlorolactone is 0.05:0.05˜0.10:3.0˜4.5:1.2˜2.0:1.0;the organic phosphine or its salt is the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate of claim 1; thearylboronic acid is R⁵C₆H₄B(OH)₂; the chemical structure of theoptically active chlorolactone is

the chemical structure of the product coupled by optically activechlorolactone and aryl boronic acid is

R⁵ is ortho-, meta-, para-substituted alkyl, alkoxy, aryl or hydrogen;R⁶ is alkyl, phenyl or heterocyclic group; R⁷ is alkyl group; saidheterocyclic group is thiophene, furan or pyridine; * is opticallyactive carbon.

The typical method to synthesize Suzuki coupling compounds can bedemonstrated by the following reaction formulas:

wherein R⁵ is ortho-, meta-, para-substituted alkyl, alkoxy, aryl orhydrogen; R⁶ is alkyl, phenyl or heterocyclic group; said heterocyclicgroup is thiophene, furan or pyridine; R⁷ is alkyl group; said base ispotassium carbonate, potassium phosphate, cesium carbonate, or cesiumchloride; said organic phosphine is the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine.

Dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate ofthe current invention can also be used in the carbon-nitrogen bondformation reaction between the inert carbon-chlorine bond and the aminesto produce aromatic secondary amines or tertiary amines.

In other words, the synthesis of said aromatic secondary or tertiaryamines is carried out under the protection of inert gases, toluene isthe solvent, dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate and palladium are the catalysts, base, organic aminesand aryl chlorides undergo reaction for 1-36 hours to obtain thecorresponding coupling compounds of aromatic secondary or tertiaryamines; the molar ratio of said base and palladium catalysts, organicphosphine or its tetrafluoroborate, organic amine and aryl chlorides is1.5˜4.0:0.01˜0.05:0.015˜0.10:1.2˜2.5:1.0; said organic solvent is1,4-dioxane or toluene; said palladium catalyst is palladium acetate ortris(dibenzylideneacetone)dipalladium (Pd₂(dba)₃.CHCl₃); base ispotassium tert-butoxide, sodium tert-butoxide, potassium phosphate,potassium hydroxide, sodium hydroxide, sodium hydride, and the basewhich can provide alkoxy anion, hydrogen anion or hydroxyl anion; theorganic phosphine or its salt is the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate of claim 1; saidaryl chloride is R⁴ substituted chlorobenzene; said organic amine is R⁸,R⁹ substituted organic primary amine and secondary amine; R⁸ is alkyl,phenyl or heterocyclic group; R⁹ is alkyl, phenyl, heterocyclic group orhydrogen; said heterocyclic group thiophene, furan or pyridine.

The typical method to produce carbon-nitrogen coupling compounds can bedemonstrated with the following formula:

According to the method to synthesize biphenyl compounds of the currentinvention, dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate, potassium phosphate, palladium acetate, arylboronicacid and arylchloride are used as starting materials. Toluene or1,4-dioxane is used as solvent. dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate is used tocoordinated with palladium catalyst in order to activate inertcarbon-chlorine bonds highly selectively to produce biphenyl compounds.The detailed steps are: 3.5 equivalent of anhydrous potassium phosphatepowder is added into the reactor. The reactor is heated under vacuum andbackfilled with inert gas for three times. After the reactor is cooledto room temperature, 0.03 equivalent of palladium acetate, 0.06equivalent of dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate, 2.0 equivalent of acrylboronic acid, 3.0 equivalentof water, 2.0 equivalent of arylchloride and 1 mL of 1,4-dioxane areadded into the reactor. The reaction is carried out at 110° C. and thereactants are stirred for 0.6-28 hours to afford corresponding biphenylcompounds.

The method to produce optically active lactone compounds is as follows:dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,potassium carbonate, palladium acetate, arylboronic acid and opticallyactive chlorolactone are used as starting materials. Toluene is solvent.Dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate isused to coordinated with palladium catalyst to activate inertcarbon-chlorine highly selectively to produce optically active lactones.The synthesis steps are as follows: with the protection of inert gas,0.05 equivalent of palladium acetate, 0.05-0.10 equivalent ofdialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,3.0-4.5 equivalents of potassium carbonate, 1.5 equivalents ofarylboronic acid, optically active chlorolactone and toluene are addedto the reactor. The reaction is carried out at 110° C. and the reactantsare stirred for 5-60 minutes to afford the corresponding couplingoptically active lactones.

The method to produce phenylamine of the current invention is asfollows: dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate, potassium tert-butoxide,tris(dibenzylideneacetone)dipalladium (Pd₂(dba)₃CHCl₃) or palladiumacetate, organic amine and arylchloride are used as starting materials.Toluene is used as the solvent. Dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate is used tocoordinated with palladium catalyst to activate inert carbon-chlorinebonds highly selectively in order to produce aromatic secondary aminesor tertiary amines. The steps are as follows: Under the protection ofinert gases, 0.05 equivalent of palladium acetate, 0.075 equivalent ofdialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,potassium tert-butoxide, arylchloride and toluene are added into thereactor. The reactants are stirred for 1-36 hours at 110° C. to affordthe corresponding coupling aromatic secondary amines or tertiary amines.

The current invention relates to a new method to synthesizedialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,and its application in the inert carbon-chlorine bond activation forSuzuki coupling reactions and the carbon-nitrogen bond formationreactions. To be more specific, the current invention relates to a newmethod to synthesize dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate which is stable in the air, and to use the highlyactive organic phosphine ligand in the reaction to coordinated withpalladium catalyst in order to activate sp² carbon-chlorine bonds highlyselectively and to catalyze the Suzuki couplings with aryl boronic acidsor carbon-nitrogen bond couplings with amines. The organic phosphinecompounds of the current invention can be used in the Suzuki couplingreactions of optically active β-chloro-α,β-unsaturated five-memberedlactones to produce the corresponding optically active products.However, two well-known organic phosphine (tricyclohexylphosphoniumtetrafluoroborate and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl)always used in carbon-chlorine bond activation would lead toracemizations.

The current invention uses only one step to synthesize dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine and its tetrafluoroborate which are stable inthe air, and develops a new type of organic phosphine compounds(dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine and its tetrafluoroborate)which has been used in highly efficient activation of inertcarbon-chlorine bonds and the applications in the inert carbon-chlorinebond for Suzuki coupling reactions and carbon-nitrogen bond formationreactions. Compared with known synthetic routes of ligands in activatingcarbon-chlorine bonds, the method of the current invention is short,easy to operate. Moreover, with this type of ligands, the Suzukicoupling products of optically active chlorolactones and arylboronicacids would maintain their configuration and optical purity.

DETAILED DESCRIPTION AND EMBODIMENTS

The following examples serve only to provide a better understanding ofthe invention without any limitation of the current invention.

Example 1 Synthesis of dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine

To a solution of trimethoxybenzene (1.0062 g, 6 mmol) in 20 mL of dryTHF was added n-butyl lithium (2.6 mL, 2.5 M in hexane, 6.6 mmol)dropwise under N₂. The mixture was stirred for 4.5 hours at roomtemperature, at which time the reaction system was then cooled to −78°C. Chlorodicyclohexyl phosphine was added dropwise. After the mixture isstirred for 30 minutes, the reaction system was warmed up to roomtemperature and stirred for another 18 hours. Extraction with ethylacetate, washed with water, dried over anhydrous sodium sulfate, andpurified by column chromatography (petroleum ether/ethylacetate=10/1˜5/1) afforded 0.5514 g of product. The yield is 25%.

¹H NMR (300 MHz, CDCl₃) δ 6.08 (d, J=1.5 Hz, 2H). 3.81 (s, 3H), 3.77 (s,6H), 2.30-2.16 (m, 2H), 1.92-1.54 (m, 8H), 1.48-0.90 (m, 12H); ³¹P NMR(121 MHz, CDCl₃) δ-14.6.

Example 2 Synthesis of dicyclohexyl(2,4,6-trimethoxyphenyl) phosphinetetrafluoroborate

To a solution of trimethoxybenzene (2.0182 g, 12 mmol, 12 mmol) in 50 mLof dry THF was added n-butyl lithium (0.8 mL, 2.5 M in hexane, 12 mmol)dropwise under N₂. The mixture was stirred for 11.5 hours at roomtemperature, at which time the reaction system was then cooled to −78°C. Chlorodicyclohexyl phosphine was added dropwise. After the mixture isstirred for 30 minutes, the temperature is warmed to room temperatureand the reaction was stirred for another 18 hours.

To another dried three-neck flask was added PCl₃ (0.92 mL, d=1.50 g/mL,1.38 g, 10 mmol) and 50 mL of dry Et₂O. The solution was cooled to −40°C. and cyclohexylmagnesium chloride (25 mL, 0.80 M, 20 mmol) was addeddropwise at this temperature within 10 min. After the addition, theresulting mixture was allowed to stir at 30° C. for 7.4 h. The aboveprepared S-trimethoxyphenyl lithium solution was then added in oneportion. After another 11.5 h with stirring at 30° C., the reaction wasquenched with 40 mL of aqueous HBF₄ (38% wt) with vigorous stirring for20 min. Water (100 mL) was added and the resulting mixture was extractedwith CH₂Cl₂ (100+50 mL), washed with 50 mL of brine, and dried overanhydrous Na₂SO₄. Filtration, evaporation and recrystallization byEt₂O/CH₂Cl₂ afforded 1.4092 g ofdicyclohexyl(2,4,6-trimethoxyphenyl)phosphine tetrafluoroborate isobtained and the yield is 31%.

m.p.: 142.6-143.4° C.; ¹H NMR (300 MHz, CDCl₃) δ 6.55 (dt, J₁=480 Hz,J₂=6.9 Hz, 1H), 6.23 (d, J=4.2 Hz, 2H), 3.90 (s, 9H), 2.80-2.58 (m, 2H),2.12-1.97 (m, 2H), 1.90-1.60 (m, 8H), 1.51-1.09 (m, 10H); ¹³C NMR (75MHz, CDCl₃) δ 168.4, 164.2, 91.5 (d, J=6.4 Hz), 78.9 (d, J=88.3 Hz),56.5, 56.1, 29.0 (d, J=45.8 Hz), 27.9 (d, J=2.1 Hz), 26.7 (d, J=3.2 Hz),25.8 (d, J=14.2 Hz), 25.6 (d, J=13.0 Hz), 24.9; ³¹P NMR (121 MHz, CDCl₃)δ 7.09; IR (KBr) v (cm⁻¹) 3417, 2933, 2854, 1599, 1577, 1468, 1452,1416, 1344, 1233, 1210, 1164, 1130, 1108, 1084; MS (70 eV, EI) m/z (%):364 (M⁺-HBF₄, 26.75), 349 (M⁺-HBF₄-Me, 7.41), 333 (M⁺-HBF₄—OMe, 31.52),309 (M⁺-BF₄—C₄H₈, 19.82), 282 (M⁺-BF₄-Cy, 100), 199 (M⁺-BF₄-2Cy, 78.01);(computed value: Anal. Calcd. For) C₂₁H₃₄BF₄O₃P, C, 55.77; H, 7.58.value measured. Found: C, 55.83; H, 7.54.

Example 3 Synthesis of dicyclohexyl(2,6-dimethoxybiphenyl) phosphinetetrafluoroborate

The synthesis is carried in the same manner as the method described inexample 2. The difference is that: the starting material istrichlorophosphine (0.92 mL, 1.38 g, 10 mmol), cyclohexylmagnesiumchloride (0.8 M in Et₂O), 1,3-Dimethoxybenzene (1.60 mL, 1.68 g, 12mmol) and n-butyl lithium (2.5 M in hexane). After the reaction is donein ether/tetrahydrofuran, tetrafluoborate aqueous solution is used toquench the reaction, and dialkyl(2,6-methoxyphenyl)phosphinetetrafluoroborate is obtained. The yield is 15%.

¹H NMR (300 MHz, CDCl₃) δ 7.63-7.71 (m, 1H), 6.80-6.65 (m, 2H), 6.77(dt, J₁=486 Hz, J₂=6.3 Hz, 1H); 3.95 (s, 6H), 2.90-2.70 (m, 2H),2.20-2.06 (m, 2H), 1.95-1.63 (m, 8H), 1.56-1.10 (m, 10H); ³¹P NMR (121MHz, CDCl₃) δ 7.36.

Example 4 Synthesis of 4-Methoxybiphenyl

To a rubber-capped Schlenk vessel was added K₃PO₄ (298.4 mg, 1.4 mmol).This equipment was dried with flame under vacuum and backfilled withnitrogen for three times. Then Pd(OAc) (2.7 mg, 0.012 mmol),dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine tetrafluoroborate (11.0mg, 0.024 mmol), phenyl bronic acid (99.8 mg, 98%, 0.80 mmol), and 0.5mL of dioxane were added sequentially to the Schlenk vessel. After beingstirred for about 5 min at room temperature, p-methoxyphenyl chloride(56.5 mg, 0.40 mmol), another 0.5 mL of dioxane, and 21.5 μL of water(21.5 mg, 1.2 mmol) were added sequentially in one portion. Theresulting mixture was heated at 110° C. with a preheated oil bath. After11 h, the reaction was complete as monitored by GC. The reaction mixturewas then cooled and diluted by 10 mL of CH₂Cl₂ and filtered through ashort column of silica gel (eluent: 2×10 mL of CH₂Cl₂). Evaporation andpurification by chromatography (petroleum ether/ether=60/1) on silicagel afforded 4-Methoxybiphenyl (65.9 mg, 90%)

m.p.: 87.2-87.8° C.; ¹H NMR (300 MHz, CDCl₃) δ 7.65-7.55 (m, 4H),7.52-7.41 (m, 2H), 7.40-7.32 (m, 1H), 7.08-7.00 (m, 2H), 3.89 (s, 3H);¹³C NMR (75 MHz, CDCl₃) δ 159.1, 140.7, 133.7, 128.7, 128.1, 126.7,126.6, 114.1, 55.3; IR (KBr) v (cm⁻¹) 3069, 3027, 3003, 2955, 2895,2829, 1606, 1522, 1488, 1464, 1288, 1270, 1251, 1201, 1184, 1035; MS (70eV, EI) m/z (%): 185 (M⁺+1, 14.24), 184 (M⁺, 100).

Example 5 Synthesis of (R)-(−)-3-propyl-4,5-diphenyl-2(5H)-furanone

Under the protection of nitrogen, phenylboronic acid (19.1 mg, 98%, 0.15mmol), palladium acetate (1.2 mg, 0.0054 mmol),dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine tetrafluoroborate (11.0mg, 0.024 mmol), potassium carbonate (63.1 mg, 0.46 mmol) and 0.5 mL ofanhydrous toluene are added sequentially to the reactor. The mixture isstirred at room temperature for 3 min and then(R)-(−)-3-propyl-4-chloride-5-phenyl-2(5H)-furanone (22.8 mg, 0.096mmol, 97% ee) and 0.5 mL of anhydrous toluene are added into thereactor. The reaction is carried out at 110° C. for 6 min and quenchedwith 10 mL of water. Extracted with ether, wash with brine, dried overanhydrous sodium sulfate, and purified by column chromatography afforded20.1 mg of (R)-(−)-3-propyl-4,5-diphenyl-2(5H)-furanone. The yield is75%, 98% ee.

HPLC condition: Chiralpak OD-H, rate: 0.8 mL/min, λ=230 nm,n-hexane/1-PrOH=65/35. m.p.: 103.8-104.9° C. (n-hexane). ¹H NMR (300MHz, CDCl₃) δ 7.37-7.15 (m, 10H), 6.16-6.14 (m, 1H), 2.58-2.42 (m, 2H),1.78-1.60 (m, 2H), 0.98 (t, J=7.4 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ174.1, 159.1, 134.9, 131.5, 129.5, 129.1, 128.7, 128.5, 127.8, 127.3,83.7, 26.3, 21.5, 14.1; IR (KBr) v (cm⁻¹) 3057, 3027, 2958, 2939, 2870,1749, 1734, 1649, 1498, 1455, 1445, 1355, 1340, 1206, 1126, 1090, 1072,1014; MS (70 eV, EI) m/z (%): 279 (M⁺+1, 16.57), 278 (M⁺, 77.10), 173(100); Anal. Calcd. for C₁₉H₁₈O₂: C, 81.99; H, 6.52. Found: C, 82.00; H,6.53. [α]²⁰ _(D)=−152.0.

Example 6 (Control example) Coupling reaction of optically active4-chloride cicrotoic acid lactone with Cy₃P HBF₄ being the ligand

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that, the reactans are(R)-(−)-3-propyl-4-chloride-5-phenyl-2(5H)— furanone (23.9 mg, 0.10mmol, 97% ee), phenylboronic acid (19.2 mg, 98%, 0.15 mmol), palladiumacetate (1.1 mg, 0.005 mmol), tricyclohexylphosphonium tetrafluoroborate(1.8 mg, 0.005 mmol), potassium carbonate (62.0 mg, 0.45 mmol) and 1 mLof anhydrous toluene. The reactants are reacted for 1 hours under 110°C., and 3-methyl-4,5-diphenyl-2(5H)-furanone is obtained. The yield is67%, 0% ee, 9% the starting material is recycled.

Example 7 (Control example) Coupling reaction of optically active4-chloride cicrotoic acid lactone using2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl as the catalyst

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that, the reactants are(R)-(−)-3-propyl-4-chloride-5-phenyl-2(5H)— furanone (22.9 mg, 0.097mmol, 97% ee), phenylboronic acid (19.0 mg, 98%, 0.15 mmol), palladiumacetate (1.1 mg, 0.005 mmol),2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (2.1 mg, 0.005 mmol),potassium carbonate (62.1 mg, 0.45 mmol) and 1 mL of anhydrous toluene.The reactants are reacted for 1 hours under 110° C., and3-methyl-4,5-diphenyl-2(5H)-furanone is obtained. The yield is 40%, <16%ee, 11% the starting material is recycled.

Example 8 Synthesis of (R)-(−)-3-propyl-4,5-diphenyl-2(5H)-furanone

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that 5%dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine is used as the ligand toreact for 5 minutes. 70% yield is achieved. 96% ee(R)-(−)-3-propyl-4,5-diphenyl-2(5H)-furanone is obtained.

Example 9 Synthesis of (S)-3-methyl-4,5-diphenyl-2(5H)-furanone

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that, the reactans are(S)-3-methyl-4-chloride-5-phenyl-2(5H)— furanone (20.2 mg, 0.097 mmol),phenylboronic acid (19.0 mg, 98%, 0.15 mmol), palladium acetate (1.1 mg,0.01 mmol), dicyclohexyl(2,4,6-trimethoxyphenyl)phosphinetetrafluoroborate (2.5 mg, 0.0055 mmol), potassium carbonate (62.3 mg,0.45 mmol) are reacted in 2 mL of anhydrous toluene at 110° C. for 6minutes and 20.1 mg (S)-3-methyl-4,5-diphenyl-2(5H)-furanone isobtained. The yield is 83%, 99% ee.

[α]²⁰ _(D)+179.5 (c=0.96, CHCl₃); liquid; ¹H NMR (300 MHz, CDCl₃) δ7.40-7.17 (m, 10H), 6.21-6.16 (m, 1H), 2.16 (d, J=1.8 Hz, 3H); ¹³C NMR(75 MHz, CDCl₃) δ 174.5, 158.3, 135.0, 131.4, 129.6, 129.2, 128.79,128.77, 128.0, 127.5, 124.1, 83.7, 10.3.

Example 10 Synthesis of(S)-(+)-3-methyl-4-(methoxyphenyl)-5-phenyl-2(5H)-furanone

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that(S)-(+)-3-methyl-4-chloride-5-phenyl-2(5H)— furanone (42.1 mg, 0.20mmol, 97% ee), methoxyphenylboronic acid (47.3 mg, 97%, 0.30 mmol),palladium acetate (2.2 mg, 0.0098 mmol),dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine tetrafluoroborate (4.6 mg,0.010 mmol), potassium carbonate (123.4 mg, 0.89 mmol) are reacted in 2mL of anhydrous toluene at 110° C. for 6 minutes and 56.5 mg of(S)-3-methyl-4-(methoxyphenyl)-5-phenyl-2(5H)-furanone is obtained. Theyield is 100%, 97% ee.

[α]²⁰ _(D)=+ 229.7 (c=1.05, CHCl₃); liquid; ¹H NMR (300 MHz, CDCl₃) δ7.32-7.19 (m, 7H), 6.90-6.83 (m, 2H), 6.18-6.13 (m, 1H), 3.78 (s, 3H),2.18 (d, J=1.5 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 174.7, 160.4, 157.6,135.4, 129.6, 129.1, 128.7, 127.5, 123.6, 122.1, 114.1, 83.4, 55.2,10.5; IR (neat) v (cm⁻¹) 3063, 3033, 3003, 2934, 2840, 1747, 1651, 1607,1572, 1515, 1456, 1421, 1383, 1343, 1295, 1256, 1182, 1095, 1035; MS (70eV, EI) m/z (%): 281 (M⁺+1, 15.43), 280 (M⁺, 78.42), 175 (100); HRMScalcd for C₁₈H₁₆O₃ (M⁺): 280.1099. Found: 280.1097.

Example 11 Synthesis of(R)-(−)-3-methyl-5-pentyl-4(methoxyphenyl)-2(5H)-furanone

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that(S)-(−)-3-methyl-5-pentyl-4-chloride-2(5H)— furanone (19.7 mg, 0.097mmol, 97% ee) and 2.0 equivalent methoxyphenyl boronic acid are used asstarting material. Under standard conditions, the yield can reach 81%,ee value is 98%, and corresponding(R)-(−)-3-methyl-5-pentyl-4(methoxyphenyl)-2(5H)-furanone is obtained.

[α]²⁰ _(D)=−268.2 (c=1.00, CHCl₃); ¹H NMR (300 MHz, CDCl₃) δ 7.31-7.21(m, 4H), 5.36-5.29 (m, 1H), 2.42 (s, 3H), 2.04 (d, J=1.8 Hz, 3H),1.85-1.75 (m, 1H), 1.49-1.31 (m, 3H), 1.31-1.10 (m, 4H), 0.83 (t, J=6.8Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 174.8, 159.5, 140.0, 129.7, 128.7,127.6, 122.8, 81.7, 33.0, 31.3, 24.1, 22.4, 21.4, 13.9, 10.0; IR (neat)v (cm⁻¹) 2955, 2927, 2860, 1752, 1656, 1614, 1515, 1454, 1383, 1337,1228, 1090, 1056; MS (70 eV, EI) m/z (%): 259 (M⁺+1, 2.67), 258 (M⁺,13.76), 159 (100); HRMS calcd for C₁₇H₂₂O₂ (M⁺): 258.1620. Found:258.1620.

Example 12 Synthesis of (S)-3-methyl-5-phenyl-4-(methoxyphenyl)-2(5H)furanone

This reaction is carried out in the same manner as the reaction inexample 5. The difference is that(S)-(+)-3-methyl-5-4-chloride-5-phenyl-2(5H)— furanone (20.1 mg, 0.096mmol, 97% ee), methoxyphenyl boronic acid (20.4 mg, 98%, 0.15 mmol),palladium acetate (1.2 mg, 0.0054 mmol),dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine tetrafluoroborate (2.2 mg,0.0049 mmol), potassium carbonate (62.8 mg, 0.46 mmol) are reacted in 1mL of toluene at 110° C. for 5 minutes and 18.3 mg of(S)-3-methyl-4-(methoxyphenyl)-5-phenyl-2(5H)-furanone is obtained. Theyield is 100%, 96% ee.

[α]²⁰ _(D)=+ 191.3 (c=0.83, CHCl₃); liquid; ¹H NMR (300 MHz, CDCl₃) δ7.31-7.12 (m, 9H), 6.20-6.16 (m, 1H), 2.32 (s, 3H), 2.16 (d, J=1.5 Hz,3H); ¹³C NMR (75 MHz, CDCl₃) δ 174.7, 158.2, 140.0, 135.3, 129.5, 129.1,128.8, 128.5, 127.9, 127.5, 123.3, 83.6, 21.3, 10.4.

Example 13 Synthesis of3-methyl-4-(methoxyphenyl)-5-phenyl-2(5H)-furanone

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 3-methyl-4-chloride-5-phenyl-2(5H)—furanone (42.0 mg, 0.2 mmol), methoxyphenyl boronic acid (46.5 mg, 97%,0.3 mmol), palladium acetate (2.3 mg, 0.01 mmol),dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine (7.3 mg, 0.02 mmol),potassium carbonate (82.3 mg, 0.6 mmol) are reacted in 1 mL of tolueneat 110° C. for 35 minutes and 3-methyl-4-(methoxyphenyl)-5-phenyl-2(5H)—furanone is obtained. The yield is 100%.

Example 14 Synthesis of 2,6-dimethyl-3′,5′-dimethoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that reactants are3,5-dimethoxychlorobenzene (169.9 mg, 0.98 mmol), 2,6-dimethoxyphenylboronic acid (332.0 mg, purity: 90%, 2.0 mmol), palladium acetate (27.mg, 0.030 mmol), dicyclohexyl(2,4,6-trimethoxyphenyl)phosphinetetrafluoborate (27.3 mg, 0.060 mmol), potassium phosphate (742.5 mg,3.5 mmol), water (54.0 pt, 3.0 mmol) and 2.5 mL of 1,4-dioxane arereacted at 110° C. for 11 hours and 223.5 mg of2,6-dimethyl-3′,5′-dimethoxydiphenyl is obtained. The yield is 94%.

¹H NMR (300 MHz, CDCl₃) δ 7.18-7.02 (m, 3H), 6.45 (t, J=2.2 Hz, 1H),6.31 (d, J=2.4 Hz, 2H), 3.76 (s, 6H), 2.08 (s, 6H); ¹³C NMR (75 MHz,CDCl₃) δ 160.8, 143.0, 141.7, 135.8, 127.1, 127.0, 106.8, 98.5, 55.1,20.5; IR (neat) v (cm⁻¹) 3057, 2999, 2955, 2835, 1592, 1455, 1421, 1377,1344, 1327, 1296, 1250, 1205, 1154, 1064, 1033; MS (70 eV, EI) m/z (%):243 (M⁺+1, 18.52), 242 (M⁺, 100).

Example 15 Synthesis of 2,6-dimethyl-3′-methoxy diphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that reactants are2,6-dimethoxychlorobenzene (139.1 mg, 0.99 mmol), 3-methoxyphenylboronic acid (313.8 mg, 97%, 2.0 mmol), palladium acetate (6.5 mg, 0.029mmol), dicyclohexyl(2,4,6-trimethoxyphenyl)phosphine tetrafluoborate(27.1 mg, 0.060 mmol), potassium phosphate (742.6 mg, 3.5 mmol), water(54.0 μL, 3.0 mmol) and 2.5 mL of 1,4-dioxane are reacted at 110° C. for11 hours and 202.8 mg of 2,6-dimethyl-3″-methoxydiphenyl is obtained.The yield is 97%.

¹H NMR (300 MHz, CDCl₃) δ 7.34-7.26 (m, 1H), 7.17-7.05 (m, 3H),6.88-6.83 (m, 1H), 6.75-6.67 (m, 2H), 3.77 (s, 3H), 2.04 (s, 6H); ¹³CNMR (75 MHz, CDCl₃) δ 159.6, 142.4, 141.6, 135.9, 129.4, 127.2, 127.0,121.3, 114.4, 112.0, 55.0, 20.7; IR (neat) v (cm⁻¹) 3063, 2999, 2954,2833, 1608, 1578, 1466, 1430, 1377, 1309, 1288, 1247, 1208, 1177, 1050,1026; MS (70 eV, EI) m/z (%): 213 (M⁺+1, 17.22), 212 (M⁺, 100).

Example 16 Synthesis of 4-methoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 0.06 equivalent ofdicyclohexyl(2,6-dimethoxyphenyl) phosphine tetrafluoborate is used ascatalyst. The reaction is carried out for 12 hours and 4-methoxydiphenylis obtained. The yield is 41%.

Example 17 Synthesis of 4-methoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 0.06 equivalent ofdicyclohexyl(2,6-diisopropyl)phosphine tetrafluoborate is used ascatalyst. The reaction is carried out for 12 hours and 4-methoxydiphenylis obtained. The yield is 100%.

Example 18 Synthesis of 4-methoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 3 equivalent of potassium carbonate isused as base. Toluene is the solvent. The reaction is carried out at110° for 28 hours and 4-methoxydiphenyl is obtained. The yield is 41%.

Example 19 Synthesis of 4-methoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 3 equivalent of potassium carbonate isused as base. The reaction is carried out at 110° for 28 hours and4-methoxydiphenyl is obtained. The yield is 88%.

Example 20 Synthesis of 4-methoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 3 equivalent of cesium fluoride isused as base. The reaction is carried out at 110° for 24 hours and4-methoxydiphenyl is obtained. The yield is 80%.

Example 21 Synthesis of 4-methoxydiphenyl

This reaction is carried out in the same manner as the reaction inexample 4. The difference is that 3 equivalent of cesium carbonate isused as base. The reaction is carried out at 110° for 13 hours and4-methoxydiphenyl is obtained. The yield is 88%.

Example 22 Synthesis of N-phenyl-N-methyl-3,5-dimethylpheylamine

Under the protection of nitrogen, palladium acetate (4.4 mg, 0.02 mmol),dicyclohexyl(2,6-dimethoxyphenyl)phosphine tetrafluoborate (14.4 mg,0.03 mmol), sodium tert-butoxide (155.1 mg, 97%, 1.6 mmol),3,5-dimethoxychlorobenzene (68.8 mg, 0.4 mmol) and 1 mL of toluene wereadded to the reactor sequentially. The mixture is stirred at roomtemperature for 4 minutes. N-methylphenyl amine (86.1 mg, 0.8 mmol) andanother 1 mL of toluene were added into the reactor. The reactor washeated to 110° C. and the temperature is maintained for 24 hours. Afterthe reactor is cooled, 10 mL of methylene dichloride was used to quenchthe reaction. Filtration and column chromatography (petroleum:ethylacetate:triethylamine=100:1:1) afforded 74.5 mg ofN-phenyl-N-methyl-3,5-dimethylpheylamine. The yield is 77%.

¹H NMR (300 MHz, CDCl₃) δ 7.38-7.29 (m, 2H), 7.16-7.10 (m, 2H),7.09-7.01 (m, 1H), 6.16 (d, J=2.1 Hz, 2H), 6.10 (t, J=2.0 Hz, 1H), 3.76(s, 6H), 3.32 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 161.3, 150.8, 148.6,129.2, 122.4, 122.3, 97.4, 92.4, 55.2, 40.3.

Example 23 Synthesis of N-phenyl-N-methyl-3,5-dimethylpheylamine

Under the protection of nitrogen, 0.05 equivalent of palladium acetate,0.075 equivalent of dicyclohexyl(2,6-diisopropyl)phosphinetetrafluoborate, 2.0 equivalent of potassium hydroxide, 1.0 equivalentof 3,5-dimethoxychlorobenzene and 1.2 equivalent of phenylamine werereacted in toluene at 110° C. for 3 hours.N-phenyl-N-methyl-3,5-dimethylpheylamine was obtained with a yield of93%.

Example 24 Synthesis of N-phenyl-N-methyl-3,5-dimethylpheylamine

Under the protection of nitrogen, 0.025 equivalent oftris(dibenzylideneacetone)dipalladium (Pd₂(dba)₃.CHCl₃), 0.075equivalent of dicyclohexyl(2,6-diisopropyl)phosphine tetrafluoborate,4.0 equivalent of potassium tert-butoxide, 1.0 equivalent of3,5-dimethoxychlorobenzene and 2.0 equivalent of phenylamine werereacted in toluene at 110° C. for 24 hours.N-phenyl-N-methyl-3,5-dimethylpheylamine was obtained with a yield of57%.

Example 25 Synthesis of N-phenyl-N-methyl-3,5-dimethylpheylamine

The reaction was carried out in the same manner as the reaction inexample 22. The difference was that 4.0 equivalent of sodium hydride wasused as base. After the reaction was carried out at 110° C. for 24hours, N-phenyl-N-methyl-3,5-dimethylpheylamine was obtained with ayield of 56%.

1-8. (canceled)
 9. A dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate, having a structure of

wherein R¹ and R² is an isopropyl, tertbutyl, cyclopropyl, cyclopentyl,cyclohexyl, or admantyl group, respectively; and R³ is an alkyl group.10. A method for preparing the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate as described inclaim 9, comprising the steps of (i) reacting an alkoxybenzene(R³O)_(n)C₆H_((6-n)) with n-butyl lithium, using tetrahydrofuran as anorganic solvent, at room temperature, for 2-15 hours to obtain a lithiumreagent (R³O)_(n)C₆H_((5-n))Li, (ii) reacting the lithium reagent(R³O)_(n)C₆H_((5-n))Li with a chlorodialkyl phosphine R¹R²PCl under−78-30° C. for 2 to 10 hours to obtain a dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine (R³O)_(n)C₆H_((5-n))P R¹R², and quenching thereaction with an aqueous solution of tetrafluoroboric acid to obtain thedialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine tetrafluoroborate((R³O)_(n)C₆H_((5-n))PR¹R²)(H⁺BF₄ ⁻), wherein molar ratio of saidchlorodialkyl phosphine to said lithium reagent is (0.8-1.2):1.
 11. Themethod for preparing the dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine orits tetrafluoroborate as described in claim 10, further comprising thestep of purifying said dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphinetetrafluoroborate ((R³O)_(n)C₆H_((5-n))P R¹R²)(H⁺BF₄ ⁻) byre-crystallization.
 12. A method for using the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate as described inclaim 9 in a selective inert carbon-chlorine bond Suzuki couplingreaction to synthesize a coupling compound or in a carbon-nitrogen bondformation reaction between an inert carbon-chlorine bond and an amine tosynthesize an aromatic secondary amine or tertiary amine.
 13. The methodfor using the dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate as described in claim 12, comprising the step ofreacting the dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate with a palladium catalyst, a base, an arylboronicacid, water, and an arylchloride under protection of an inert gas, at80-120° C., in an organic solvent, for 0.6-28 hours, to obtain abiphenyl coupling compound, wherein said organic solvent is 1,4-dioxaneor toluene; molar ratio of said base, said palladium catalyst, saiddialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,said arylboronic acid, water, and said arylchloride is(2.0˜4.0):(0.03˜0.05):(0.06˜0.10):(1.5˜2.5):(0˜5.0):1.0; said base ispotassium carbonate, potassium phosphate, cesium carbonate, or cesiumfluoride; said arylchloride is an R⁴-substituted chlorobenzene

said arylboronic acid is R⁵C₆H₄B(OH)₂; R⁴ is an ortho-, meta-, orpara-substituted alkyl, alkoxy, or hydrogen; and R⁵ is an ortho-, meta-,or para-substituted alkyl, alkoxy, aryl, or hydrogen.
 14. The method forusing the dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate as described in claim 12, comprising the step ofreacting palladium acetate, the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate, potassiumcarbonate, an arylboronic acid, and an optically active chlorolactoneunder protection of an inert gas, at a temperature of 80-120° C., usingtoluene as a solvent, for 5-60 minutes to obtain a coupling opticallyactive lactone compound, wherein molar ratio of said palladium acetate,said dialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or itstetrafluoroborate, said potassium carbonate, said arylboronic acid, andsaid optically active chlorolactone is0.05:(0.05˜0.10):(3.0˜4.5):(1.2˜2.0):1.0; the arylboronic acid isrepresented by formula R⁵C₆H₄B(OH)₂; said optically active chlorolactoneis represented by formula

R⁵ is an ortho-, meta-, or para-substituted alkyl, alkoxy, aryl, orhydrogen; R⁶ is an alkyl, aryl, or heterocyclic group; R⁷ is an alkylgroup; said heterocyclic group is thiophene, furan, or pyridine; and *is an optically active carbon.
 15. The method for using thedialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate asdescribed in claim 12, comprising the step of reacting saiddialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate, apalladium catalyst, a base, an organic amine, and an aryl chloride underprotection of an inert gas, in an organic solvent, for 1-36 hours toobtain a coupling compound that is a secondary or tertiary aromaticamine, wherein molar ratio of said base, said palladium catalyst, saiddialkyl(2,4,6- or 2,6-alkoxyphenyl)phosphine or its tetrafluoroborate,said organic amine, and said aryl chloride is(1.5˜4.0):(0.01˜0.05):(0.015˜0.10):(1.2˜2.5): 1.0; said organic solventis 1,4-dioxane or toluene; said palladium catalyst is palladium acetateor tris(dibenzylideneacetone)dipalladium; said base is potassiumtert-butoxide, sodium tert-butoxide, potassium phosphate, potassiumhydroxide, sodium hydroxide, sodium hydride, or a base which provides analkoxy anion, hydrogen anion, or hydroxyl anion; said aryl chloride isan R⁴ substituted chlorobenzene

R⁴ is an ortho-, meta-, or para-substituted alkyl, alkoxy, or hydrogen;said organic amine is an R⁸, R⁹-substituted organic primary amine orsecondary amine having a formula

R⁸ is an alkyl, phenyl, or heterocyclic group; R⁹ is an alkyl, phenyl,heterocyclic group, or hydrogen; said heterocyclic group is thiophene,furan, or pyridine.
 16. The method for using the dialkyl(2,4,6- or2,6-alkoxyphenyl)phosphine or its tetrafluoroborate as described in 14,wherein said coupling optically active lactone compound has maintainedits configuration and optical purity and is represented by a formula

wherein R⁵ is an ortho-, meta-, or para-substituted alkyl, alkoxy, aryl,or hydrogen; R⁶ is an alkyl, phenyl, or heterocyclic group; R⁷ is analkyl group; * is an optically active carbon; said heterocyclic group isthiophene, furan, or pyridine.